It is well recognized that the thick ascending limb of Henle'e loop is the major active component affecting both urinary concentration and dilution and it is thus a major factor in the regulation of body water balance. In spite of its importance, few studies of transport in the thick ascending limb and the factors which might regulate its function have been carried out. The past difficulties in the study of the thick ascending limb have been overcome by the use of the perfused tubule technique and recent evidence suggests that two hormones, vasopressin and prostaglandins, might play a role in the regulation of sodium chloride absorption by this segment of the nephron. Prostaglandins inhibit sodium chloride absorption while vasopressin enhances it, a competitive role which is analagous to their effects on water permeability in the collecting tubule. The action of vasopressin may be central to the effects of adrenal steroid hormones, potassium depletion, and water diuresis on urinary concentration. Steroid hormones and potassium depletion are known to affect the water permeability response to vasopressin in some tissues, but the effect in vivo is not clearly due to an impaired water permeability response. An effect on the vasopressin-responsiveness of the thick ascending limb, rather than the collecting tubule, might provide an alternative, or at least accessory, explanation for the in vivo results. I therefore propose to examine the role of vasopressin in the regulation of chloride transport by the thick ascending limb utilizing the perfused tubule technique. The effect of vasopressin on transport will be defined by a further examination of the effect of vasopressin on the transport of individual ions, on the respective ion permeabilities, and on the ion dependence of the observed transport. The effects of water diuresis, adrenal steroids, and potassium depletion per se and their effects on the vasopressin responsiveness of the thick ascending limb will be examined in vitro, using both the electrical potential and ion transport to assess the results.